It is proposed to study further in normal subjects, hypertensive subjects, cirrhotic patients and others, the interaction of angiotensin II vascular sensitivity and angiotensin II in determining levels of plasma renin activity and blood pressure. A unifying hypothesis is presented to explain the results. Studies will involve infusions and measurements of angiotensin II (AII), 1-sar-8-ala-AII (saralasin), the AII analogue which acts like AII (partial agonist) on vascular systems with increased pressor sensitivity to AII and as a antagonist of AII under conditions of decreased vascular sensitivity to AII, and finally in animal work to study the effects of beta-aminopropionitrile, an inhibitor of vascular callagen synthesis, on renin release and sodium excretion. These studies would include pathophysiological features by relating the level of blood pressure to the normal or abnormal relation of plasma renin activity and AII vascular sensitivity. Therapeutic aspects of blood pressure measurement would include effects of chronic (73 months) diuretic therapy and vasodilator therapy on vascular sensitivity to AII, plasma renin levels, and blood pressure response to saralasin. It is anticipated that a better understanding of the role of angiotensin II vascular sensitivity in blood pressure control should facilitate the measurement and guide the development of new drugs in treating hypertension in the future.